The University of Chicago Comprehensive Cancer Center (UCCCC) is submitting this competitive renewal application for its Cancer Center Support Grant for Years 38-42. The mission of the UCCCC is to elucidate the determinants of cancer, to develop cures for cancer, and to prevent cancer. Our cancer research programs emphasize translational and interdisciplinary research, and we pursue this goal by promoting collaboration among a diverse and dedicated team of outstanding basic, translational, clinical, and population researchers. The 210 members of the UCCCC are organized into six established programs, all with a translational focus (Molecular Mechanisms of Cancer; Hematopoiesis and Hematologic Malignancies; Immunology and Cancer; Pharmacogenomics and Experimental Therapeutics; Advanced Imaging; and Cancer Prevention and Control). Clinical research is a major focus of multidisciplinary activity at the UCCCC. In 2011, 876 individual patients were accrued to therapeutic protocols supported, in part, by NCI cooperative agreements and contracts to conduct Phase I, Phase II, and Phase III clinical trials. The UCCCC is a full member of the Alliance (formerly members of Cancer and Leukemia Group B and American College of Surgeons Oncology Group), the Gynecologic Oncology Group, and the Children's Oncology Group, and participates in the Radiation Therapy Oncology Group, and National Surgical Adjuvant Breast and Bowel Program studies. Funds are requested in this application for Senior Leaders and Program Leaders, Planning and Evaluation, Developmental Funds, Administration, Protocol-Specific Research, the Protocol Review and Monitoring System, Staff Investigators, and 11 shared resources (Biostatistics; Cancer Clinical Trials Office; Cytometry and Antibody Technology; Genomics; Human Immunologic Monitoring and cGMP; Human Tissue Resource Center; Image Computing, Analysis, and Repository; Integrated Microscopy; Integrated Small Animal Imaging Research Resource; Pharmacology; and Transgenic Mouse/Embryonic Stem Cell Facilities). In the period since the last review (2008-2011), the UCCCC has increased its peer-reviewed funding by 27% to $68.9 million in direct costs (NCI funding has increased by 17% from $18 to $21 million in direct costs), and contributed 1,850 peer-reviewed publications. Through an in-depth institutional review and multi-faceted strategic planning process, the UCCCC now has new and strong institutional commitments, and a stable and experienced leadership team, and has developed and implemented a comprehensive strategic plan, and restructured its Research Programs.